Advertisment Novartis
Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
Users online: 584  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page

Table of Contents 
Year : 2017  |  Volume : 62  |  Issue : 2  |  Page : 158-167
Oral and cutaneous lymphomas other than mycosis fungoides and sézary syndrome in a mexican cohort: Recategorization and evaluation of international geographical disparities

1 Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, City, Mexico
2 Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, City, Mexico
3 Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; Department of Dermatology, Cutaneous Hematopathology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, City, Mexico
4 Department of Dermatology, Dermatology Private Practice, Hospital Médica Sur, City, Mexico
5 Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; Division of Pathology, Instituto Nacional de Cancerología, City, Mexico

Date of Web Publication9-Mar-2017

Correspondence Address:
Carmen Lome-Maldonado
Division of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan, Seccion XVI, 14080 Mexico City
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.IJD_34_17

Rights and Permissions


Background: Nonmycosis fungoides/Sézary syndrome (non-MF/SS) primary cutaneous lymphomas (PCL) are currently categorized under the 2005-World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for PCL. These differ in behavior from secondary cutaneous lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid neoplasms. Aims: This study aims to report the first series of non-MF/SS PCL, SCL, and POL in a Mexican cohort, examine the applicability of current classification systems and compare our findings with those from foreign cohorts. Materials and Methods: Eighteen non-MF/SS PCL, four SCL, and two POL with available tissue for morphology and immunophenotypic assessment were reclassified according to the 2005-WHO/EORTC and 2016-WHO classifications. Results: Non-MF/SS PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative disorders predominated, followed by Epstein–Barr virus-induced lymphomas, and peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell lymphomas (BCL) were primarily of follicle center cell origin followed by postgerminal lymphomas of the diffuse large BCL variety. Conclusions: Most non-MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases. The relative frequencies in our cohort hold closer similarities to Asian registries than from those of Europe/USA, supporting the concept of individual and/or racial susceptibility, and the notion of geographical variances in the rate of lymphomas. In particular, such disparity may arise from viral-induced lymphomas which might show partial geographical restriction.

Keywords: Primary cutaneous lymphomas, primary oral lymphomas, secondary cutaneous lymphomas

How to cite this article:
Hernández-Salazar A, García-Vera JA, Charli-Joseph Y, Ortiz-Pedroza G, Méndez-Flores S, Orozco-Topete R, Morales-Leyte AL, Domínguez-Cherit J, Lome-Maldonado C. Oral and cutaneous lymphomas other than mycosis fungoides and sézary syndrome in a mexican cohort: Recategorization and evaluation of international geographical disparities. Indian J Dermatol 2017;62:158-67

How to cite this URL:
Hernández-Salazar A, García-Vera JA, Charli-Joseph Y, Ortiz-Pedroza G, Méndez-Flores S, Orozco-Topete R, Morales-Leyte AL, Domínguez-Cherit J, Lome-Maldonado C. Oral and cutaneous lymphomas other than mycosis fungoides and sézary syndrome in a mexican cohort: Recategorization and evaluation of international geographical disparities. Indian J Dermatol [serial online] 2017 [cited 2018 Jan 19];62:158-67. Available from:

What was known?

  • The relative incidence of primary cutaneous lymphoma variants has been widely described in European and North American Anglo-Saxon Countries while little is known regarding the rate of secondary cutaneous and primary oral lymphomas. By contrast, no such studies have been conducted thus far in Mexico.

   Introduction Top

Classification of lymphomas, particularly of primary cutaneous lymphomas (PCL), has dramatically evolved over the last decades due to advances in the characterization of their clinical, morphological, immunophenotypic, and molecular features.[1],[2],[3],[4],[5],[6] PCL are lymphomas occurring solely in the skin after a complete staging evaluation has ruled out extracutaneous involvement, differing in biological behavior from systemic lymphomas with secondary cutaneous dissemination (secondary cutaneous lymphomas [SCL]).[4] The 2005-World Health Organization/European Organization for the Treatment and Research of Cancer (WHO/EORTC) classification for PCL includes 13 specific entities, subcategorized into those of indolent, intermediate, or aggressive clinical behavior.[4],[5] These comprise a heterogeneous group of clonal neoplasms with protean manifestations, arising from skin-homing T-/natural killer (NK)-, B- or precursor-lymphocytes which albeit their rarity, represent the second most common form of extranodal lymphomas (19%), following those of the gastrointestinal tract. Their reported incidence among European countries is 1:100,000 persons/year, whereas recent studies in the USA suggest an incidence as high as 10.7:100,000 persons/year, with increased prevalence among non-Hispanic whites.[7],[8],[9],[10]

In contrast to nodal lymphomas, where B-cell lymphomas (BCL) outnumber T-cell lymphomas (TCL), PCL are mainly derived from T-cells (65%–80%) with primary cutaneous-BCL (PC-BCL) in the minority (20%–29%). Among well-defined PC-TCL, mycosis fungoides/Sezary syndrome (MF/SS) and CD30+ lymphoproliferative disorders (lymphomatoid papulosis [LyP] and anaplastic large cell lymphoma [ALCL]) embody most cases; 55% of PC-BCL fall under the indolent category (follicle center BCL and marginal zone lymphoma), and approximately 40% represent intermediate lymphomas of the diffuse large BCL (DLBCL) variant.[7],[8],[9],[10] Oral cavity lymphomas are scarcer than PCL, with scant reports and lack of consensus regarding a specific classification for primary oral lymphomas (POL).[11],[12],[13],[14],[15],[16],[17],[18],[19]

The incidence and clinical-histopathological features of non-MF/SS PCL and POL in Latin America, and particularly Mexico, is largely unknown. In this paper, we reviewed oral and cutaneous lymphomas (primary and secondary) other than MF/SS, which presented to our institution over a 24-year period and recategorized them according to the 2005-WHO/EORTC [4],[5] and 2016-WHO classifications.[20] To the best of our knowledge, this paper represents the first Mexican series from a single referral center using such classification systems. Finally, we compare our findings to those deriving from foreign cohorts and analyze gross geographical differences.

   Materials and Methods Top

Skin and oral biopsies diagnosed as oral or non-MF/SS cutaneous lymphoma over a 24-year period (1988–2012) were retrieved from the pathology archive of Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, after approval by the Institutional Committee for Medical Ethics. Only cases with sufficient tissue available for adequate assessment of morphological and immunophenotypic features were included in the study. Clinical information was obtained through medical records and phone interviews when necessary for data confirmation. Formalin-fixed paraffin-embedded tissue (FFPET) sections were stained with hematoxylin and eosin. Immunophenotyping with a comprehensive panel of stains was performed under standard procedures on FFPET, using commercially purchased primary antibodies according to the diagnostic possibilities for each case, concurring with the 2005-WHO/EORTC and the 2016-WHO classification criteria.[4],[5],[20] In situ hybridization (ISH) for Epstein–Barr virus (EBV) encoding region (EBER) and kappa/lambda immunoglobulin light chains were performed when deemed necessary in a case-by-case basis. Skin lymphomas were typified as PCL if no lymph node or visceral involvement was present at diagnosis, after performing a complete staging evaluation (physical examination, head to pelvis computed tomography, and bone marrow biopsy). The same staging criteria were used to designate POL.

   Results Top

Seventy-eight non-MF/SS oral and cutaneous lymphomas were identified. Twenty-four (30%) fulfilled inclusion criteria for proper recategorization; of these, 18 (75%) were skin-limited (PCL), 4 (16%) represented SCL [Table 1] and [Table 2], and 2 (8%) POL [Table 3].
Table 1: Clinical and immunohistochemical features of non-mycosis fungoides/Sézary syndrome primary cutaneous lymphomas

Click here to view
Table 2: Clinical and immunohistochemical features of lymphomas from the oral cavity

Click here to view
Table 3: Clinical and immunohistochemical features of secondary cutaneous lymphomas

Click here to view

Non-mycosis fungoides/Sézary syndrome primary cutaneous lymphomas

Non-MF/SS PC-TCL outnumbered PC-BCL (11 cases, 61% vs. 7, 39%). Non-MF/SS PC-TCL were categorized as follows: three CD30+ lymphoproliferative disorders (two LyP and one PC-ALCL), one subcutaneous panniculitis-like TCL (SPLTCL), two PC-NK/TCL, one hydroa vacciniforme-like lymphoproliferative disorder (HVLLPD), one aggressive epidermotropic CD8+ TCL (PC-AECD8+ TCL), one gamma/delta TCL (PC-GD-TCL), and two peripheral TCL, not otherwise specified (PC-PTCL-NOS). PC-BCL were primarily of follicle center cell origin: four cases (57%) of follicle center lymphoma (PC-FCL), three cases (43%) of PC-DLBCL further subdivided into two of leg type variety and one EBV+ DLBCL NOS.

Clinical features

Non-MF/SS PCL occurred in 12 males and 6 females. Age range at diagnosis was 19–67 years (mean 44 years), similar in all subgroups of non-MF/SS PCL. These arose primarily in a single anatomic region (13/18, 72%) such as trunk (4/13), extremities (4/13), head (3/13), or genital skin (2/13). Two regions were involved in 4/18 cases (22%): trunk and extremities (2), trunk and head (1), head and extremities (1). Only one case, corresponding to HVLLPD, presented with skin lesions extending to all body segments (except palms and soles), accentuated on sun-exposed areas. Most non-MF/SS PCL had more than one clinical morphology (12/18, 66%) as red or red-violaceous nodules (11) and/or infiltrated plaques (8), commonly developing secondary ulceration (6). Less frequent morphologies were recurring “waxing and waning” papules (in two patients with LyP), facial edema, hemorrhagic vesicles, small crusted ulcers and smallpox-like scars (in HVLLPD), flaccid bullae progressing to large ulcers (in a patient with PC-AECD8+ TCL), and ulcers without preceding nodules or plaques (in a patient with DLBCL-NOS).

Histopathologic and immunohistochemical features

Primary cutaneous CD30+ lymphoproliferative disorders

Both LyP cases showed a perivascular wedge-shaped dermal infiltrate with scant to moderate epitheliotropism (epidermotropism and folliculotropism). Clusters of large atypical lymphocytes were evident amidst a background of inflammatory cells (small lymphocytes, eosinophils, and few neutrophils). Large lymphocytes comprised <30% of the infiltrate and displayed CD30 expression, both co-expressed CD3 and CD25, one was CD4+ and the other CD8+ [Figure 1]. On morphological and immunophenotypical correlation, the former case would best fit with LyP Type A, the latter with LyP Type D.
Figure 1: Lymphomatoid papulosis. (a) Agminated erythematous papules on the trunk, (b) superficial wedge-shaped dermal infiltrate with moderate epidermotropism (H and E, ×40), (c) membranous immunoreactivity among small and large lymphocytes with anti-CD8 antibodies (×400), (d) large lymphocytes are immunoreactive with anti-CD30 antibodies (×400)

Click here to view

The infiltrate of PC-ALCL consisted of diffuse sheets of large pleomorphic cells extending through the dermis and into the subcutis without a significant inflammatory infiltrate. Large CD30+ cells comprised over 75% of the infiltrate, and displayed an activated Th2 CD4+ immunophenotype, without anaplastic lymphoma kinase-1 or EMA (Epithelial Membrane Antigen) expression [Figure 2].
Figure 2: Primary cutaneous anaplastic large cell lymphoma. (a). Large ulcerated tumor involving the lower extremity, (b) diffuse dermal infiltrate by large mononuclear cells underlying marked acanthosis (H and E, ×100), (c) large atypical mononuclear cells with prominent nucleoli (H and E, ×400), (d) diffuse immunopositivity with anti-CD3 antibodies (×100), (e) diffuse expression of CD30 among large neoplastic cells (×200)

Click here to view

Subcutaneous panniculitis-like T-cell lymphoma

SPLTCL was characterized by a lobular panniculitic-like infiltrate of variably sized mononuclear cells, with pronounced atypia particularly among lymphocytes surrounding individual fat cells (adipocyte rimming). Neoplastic cells displayed a cytotoxic T-cell immunophenotype with expression of CD8, TIA-1, and a high Ki-67 proliferation index, especially around individual fat cells. Furthermore, an α/β+ phenotype was confirmed by βF1 immunoreactivity. Features common to lupus panniculitis (lymphoid follicles, dermal-epidermal interface alteration, or hyalinization of fat cells) were absent [Figure 3].
Figure 3: Subcutaneous panniculitis-like T-cell lymphoma. (a) Erythematous and indurated deep-seated nodule involving left cheek, (b) pleomorphic mononuclear infiltrate exclusively involving adipose lobules (H and E, ×100), (c) prominent adipocyte rimming by atypical lymphocytes (H and E, ×200), (d) membranous immunoreactivity with anti-CD8 antibodies among neoplastic lymphocytes (×200)

Click here to view

Primary cutaneous aggressive cytotoxic lymphomas

PC-GD-TCL showed diffuse infiltrates occupying not only the subcutaneous tissue (as in SPLTCL) but involving dermis and epidermis (with marked epidermotropism). Dermal necrosis and angioinvasion were conspicuous. Mononuclear cells were medium-large, showed extensive karyorrhexis, and profound adipocyte rimming without hemophagocytosis. Neoplastic cells were EBER and CD4- but expressed CD8, CD3, CD56, and TIA-1. A γ/δ+ phenotype was confirmed by GM1 immunoreactivity and negativity for βF1.

Infiltrates in both PC-NK/TCL revealed a diffuse pandermal proliferation of lymphocytes with partial subcutaneous involvement, prominent angiocentricity, focal angiodestruction, and scant epidermotropism. Neoplastic cells were variable in size, pleomorphic, and expressed of CD3ε, CD2, CD56, cytotoxic proteins (TIA-1, granzime B, and perforin), and EBV clonal integration (EBER+) [Figure 4].
Figure 4: Primary cutaneous extranodal natural killer/T-cell lymphoma. (a) Indurated and ulcerated erythematous plaque involving nose, left eyelids, and cheek, (b) diffuse dermal and subcutaneous infiltrate with prominent angiocentricity and angiodestruction (H and E, ×40), (c) immunopositivity with anti-CD3 antibodies (×100), (d) prominent expression of cytotoxic proteins (granzyme B) among neoplastic cells (×100), (e) strong immunoreactivity with anti-CD56 antibodies (×200), (f) nuclear expression of Epstein–Barr virus RNA by in situ hybridization (EBER, ×100)

Click here to view

PC-AECD8+ TCL was characterized by a superficial and deep dermal, angiocentric, and angiodestructive lymphoid proliferation with marked epidermotropism and focal adnexal destruction. Neoplastic cells were pleomorphic and displayed a CD8+ cytotoxic phenotype immunopositive for CD3, CD45RA, granzyme B, perforin, TIA-1, and βF1 [Figure 5].
Figure 5: Primary cutaneous aggressive epidermotropic CD8 + T-cell lymphoma. (a and b) Disseminated flaccid bullae progressing to large ulcers, (c) prominent epidermotropism by atypical lymphocytes (H and E, ×400), (d) neoplastic epidermotropic lymphocytes show strong immunoreactivity with anti-CD8 antibodies (×400)

Click here to view

Hydroa vacciniforme-like lymphoproliferative disorder

HVLLPD showed an infiltrate histopathologicaly indistinguishable from PC-NK/TCL albeit less dense, in the previously described peculiar clinical scenario. As in PC-NK/TCL, the proliferation occupied the entire dermis with prominent angiocentricity, focal angiodestruction, and scant epidermotropism. Neoplastic cells were medium-large, pleomorphic, and showed immunoreactivity to CD3, CD2, CD8, CD56, cytotoxic proteins (TIA-1, granzyme B, perforin), and EBER+ [Figure 6].
Figure 6: Hydroa vacciniforme-like lymphoproliferative disorder. (a) Facial edema, hemorrhagic vesicles, small crusted ulcers, and smallpox-like scars involving sun-exposed skin, (b and c) superficial perivascular infiltrate with scant epidermotropism, comprised medium-sized pleomorphic cells (b: H and E, ×100 and c: H and E, ×200), (d) neoplastic cells are immunopositive with anti-CD8 antibodies (×100), (e) nuclear expression of Epstein–Barr virus RNA by in situ hybridization (EBER, ×100)

Click here to view

Primary cutaneous peripheral T-cell lymphomas, unspecified

Biopsies from PC-PTCL-NOS showed nonepidermotropic diffuse dermal proliferations of medium-large mononuclear T-cells. However, clinical-pathological and immunohistochemical correlations excluded them of any specific lymphoma category. Neoplastic cells displayed a double positive (CD4+/CD8+) T-cell phenotype without loss of PAN-T-cell antigen expression.

Primary cutaneous B-cell lymphomas

Infiltrates in PC-FCL cases displayed either a nodular or diffuse pattern of dermal involvement and were characterized by a mixed neoplastic population comprised chiefly of centrocytes (medium-sized lymphocytes with indented nuclei) with some admixed centroblasts (medium to large lymphocytes with peripheral nucleoli). No significant aggregates of plasma cells were observed. Independent of their morphology, neoplastic cells were positive for CD20, germinal center cell immunoreactants (BCL6 +/− CD10), and lacked expression of BCL2 and MUM-1 [Figure 7].
Figure 7: Primary cutaneous follicle-center lymphoma. (a) Multinodular erythematous plaque involving scalp, forehead, and right cheek, (b) superficial and deep dermal nodular infiltrate by mononuclear cells (H and E, ×40), (c) neoplastic lymphocytes are predominantly small to mid-sized lymphocytes with indented nuclei (centrocytes) (H and E, ×200)

Click here to view

DLBCL leg type (DLBCL-LT) were characterized by diffuse pandermal neoplastic infiltrates with subcutaneous extension, forming sheet-like aggregates of immunoblasts (large lymphocytes with a single central nucleolus) admixed with fewer centroblasts. Neoplastic cells showed a postgerminal B-cell phenotype expressing CD20, CD79a, MUM-1, and BCL2 while lacking immunoreactivity for germinal center cell markers [Figure 8].
Figure 8: Primary cutaneous diffuse large B-cell lymphoma, leg type. (a) Multinodular erythematous plaque involving the lower extremity of an elderly woman, (b and c) pandermal and subcutaneous nonepidermotropic infiltrate by large round atypical cells (H and E, ×40 and × 100 respectively)

Click here to view

Our DLBCL-NOS was morphologically indistinguishable from the former (DLBCL-LT), displayed a postgerminal B-cell immunophenotype with diffuse expression of CD20 and MUM-1, without BCL2, BCL6, and CD10 expression. In addition, EBER positivity, along with the disease developing in an elderly patient suggested this case would best fit with EBV + DLBCL NOS.

Systemic lymphomas with secondary cutaneous dissemination

Four cases of SCL included one case each of extranodal NK/TCL nasal type (EN-NK/TCL, nt), nodal PTCL-NOS, Hodgkin's lymphoma (HL), and follicular lymphoma (FL).

Clinical features

SCL occurred in two men and two women. Mean age range at diagnosis was 61.7 years. On presentation, EN-NK/TCL, nt extensively involved facial skin, nasal mucosa, and hard palate as erythematous-indurated plaques with secondary ulceration; the remaining 3 SCL were nodal lymphomas with concomitant skin involvement manifested as disseminated firm papules (HL), infiltrated plaques with alopecia (FL), and red to purple macules (PTCL-NOS). As opposed to PCL, all patients manifested B-signs including fever, weight loss, and/or palpable lymphadenopathy.

Histopathologic and immunohistochemical features

The histology and immunophenotype from cutaneous infiltrates of SCL were similar to their primary counterparts. Our single case of EN-NK/TCL, nt was indistinguishable from our PC-NK/TCL as was FL with the previously portrayed cases of PC-FCL except for BCL2 co-expression by neoplastic cells in FL. HL was characterized by a mixed tumoral/reactive dermal infiltrate where neoplastic cells comprised <10% of the infiltrate. These were large, atypical, with abundant amphophilic cytoplasm, bilobed nuclei, multiple nucleoli (Reed–Sternberg cells), and CD30/CD15+. PTCL-NOS was characterized by a nodular dermal infiltrate of medium-large pleomorphic lymphocytes with conspicuous expression of CD4, sporadic CD8 immunoreactivity, and negativity for CD7, CD30, CD15, CD56, and follicular helper T-cell markers (CD10, CXCL13).

Primary oral lymphomas

Two cases of POL were observed (65-year-old woman, 67-year-old man), and subclassified, respectively, as one extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and one PTCL-NOS. Clinically, the former appeared as a nodular, ulcerated tumor in the soft palate, whereas the latter as a multinodular erythematous plaque involving the oral mucosa and upper lip.

MALT lymphoma was characterized by a submucosal nodular lymphoid proliferation with perivascular accentuation, composed of small-sized cells with indented nuclei and prominent cytoplasm (centrocyte-like marginal zone cells), occasional lymphoplasmacytic cells, peripheral aggregates of plasma cells, and few large-sized cells similar to centroblasts [Figure 9]. In addition, an admixed reactive infiltrate of small T-cells was apparent as were few reactive germinal centers. Neoplastic marginal zone and lymphoplasmacytic cells expressed B-cell antigens (CD20, CD79a) and BCL2, while plasma cells were CD138+ showing light chain restriction on kappa/lambda ISH. Cells within reactive germinal centers expressed BCL6 and CD10, lacked BCL2, and had a high Ki-67 proliferation index.
Figure 9: Primary oral extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. (a) erythematous, indurated, and ulcerated plaque involving the soft palate, (b) multinodular submucosal mononuclear infiltrate (H and E, ×40), (c) perivascular infiltrate composed primarily of mid-sized indented lymphocytes, i.e., centrocyte-like marginal zone cells (H and E, ×200)

Click here to view

Primary oral PTCL-NOS showed a nodular submucosal infiltrate of small-medium pleomorphic T-cells with a double positive (CD4+/CD8+) immunophenotype, without CD30 expression, EBER positivity or loss of PAN-T-cell antigens.

   Discussion Top

Current epidemiological data on PCL derive mainly from experience of European and Anglo-Saxon North American countries, being scant elsewhere, particularly in Latin America. Nonetheless, geographical disparities in the incidence of lymphoma subtypes have been documented which may shed light on the pathogenesis of some lymphoma variants and potentially relate to the unequal prevalence of viral carcinogens, other currently unidentified environmental factors, and ethnic and/or genetic susceptibility factors.[21],[22],[23],[24],[25],[26],[27]

Differences in the incidence, clinical, and histopathological features of MF among Latino patients living in the USA, as compared to Caucasians, have been described in large retrospective studies (lower incidence rates, higher prevalence of early-onset disease with associated worse prognosis, and higher rates of the hypopigmented variant);[28],[29],[30] however, little is known regarding non-MF/SS PCL among native Latin Americans. To date, only a handful of studies on the descriptive epidemiology of PCL have been conducted in Latin America (mainly Brazil, Peru, and Argentina),[31],[32],[33],[34],[35],[36],[37],[38],[39],[40] and not, to the best of our knowledge, in Central and Northern Latin America where ethnicity and incidence of EBV and human T-cell leukemia virus I/II (HTLV-I/II) seropositivity substantially differ.

In our cohort, the mean age at diagnosis was lower than reported elsewhere, similarly to what is described for Latino patients with MF living in the USA.[30] While only one-third of the non-MF/SS PCL in our laboratory could be properly reclassified due to limited tissue availability, the frequency of lymphoma variants seems to differ in some aspects from both European/USA and South American registries.[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42] As in other international cohorts, non-MF/SS PC-TCL outnumbered PC-BCL. The former was led by CD30+ lymphoprolifeative disorders, in accordance with other international reports,[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41] followed closely by EBV-related NK/T-cell malignancies (PC-NK/TCL and HVLLPD), commonly reported in Asia and Central America but exceptionally in Europe and the USA.[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[43],[44],[45],[46],[47],[48] This comparatively higher frequency could potentially be explained by previously described higher prevalence of EBV subtypes associated to human pathology in developing countries and plausibly to the onset of infection at an earlier age.[49] The same argument could hold true, to the existence of one case of EBV+ DLBCL NOS among our small cohort of 7 PC-BCL, reportedly one of the rarest entities among all PCL. By contrast, no cases of adult T-cell leukemia/lymphoma (ATCLL) were observed in keeping with a practically null incidence of HTLV-I/II in studies across Mexico, including Mexico City Greater-Metropolitan Area.[50],[51],[52],[53] This contrasts with the higher frequency of HTLV-I/II seropositivity and the prevalence of ATCLL reported among Asians and South Americans (namely Brazil).[54],[55],[56]

PC-FCL was the most frequently identified PC-BCL in our cohort, in accordance with international registries. Surprisingly, no cases of PC-MZL were observed despite being reported as the second most common form of PC-BCL in European, USA, and South American studies, and speculated to be closely linked in its pathogenesis to microbial and/or autoimmune antigenic triggers, with potential geographical restrictions.[8],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48] This apparent null incidence in our cohort could be artificial; however, since PC-MZL was recently described, and formerly reported in our institution as B-cell predominant cutaneous pseudolymphoma (cutaneous lymphoid hyperplasia) before ISH for immunoglobulin light chains became available. Similarly, our cohort lacks cases of PC CD4+ small/medium T-cell lymphoproliferative disorder which until recently would have likely been diagnosed in our institution as pseudolymphomatous folliculitis but is thought to represent one of the most common non-MF/SS PCL in some recent series.[57],[58],[59]

All PCL in our cohort displayed classical histopathological and immunophenotypical features in accordance with the WHO/EORTC criteria and all but three showed the typical clinical features and behavior.[4],[5] One was a case [60] of PC-NK/TCL with prolonged survival (>60 months), manifesting initially as vulvar and perianal ulcers, and recurring postradiotherapy and chemotherapy as necrotic ulcers involving one earlobe. While EBV+ mucocutaneous ulcer was considered as an alternative diagnosis, the young age of the patient, absence of immunosuppression, presence of extragenital ulcers, and finally, conspicuous evidence of angiodestruction and pleomorphism strongly favored the diagnosis of PC-NK/TCL. Similarly, a case of PC-GD-TCL presented with topographic restriction to genital skin before progressing into disseminated disease. Finally, a case of PC-AECD8+ TCL was atypical in its clinical similarity with pemphigus vulgaris given the presence of flaccid bullae although the neoplasm behaved in the classical aggressive fashion with the patient perishing few weeks after diagnosis.

In contrast to PCL, the clinical and histopathological features of SCL remain poorly understood with very few studies from Northeast Asia and the USA.[30],[61] In the largest retrospective review from Korea, SCL consisted of mature NK/TCL (56%), mature BCL (35%), immature hematopoietic malignancies (8%), and HL (1%).[61] In our very small cohort, half of SCL were mature NK/TCL (1 EN-NK/TCL, 1 PTCL-NOS), with one case each of mature BCL (DLBCL) and HL. While the small number of SCL in our study impede meaningful comparisons with previous series, it suggests a closer distribution trend with Asian registries as opposed to population-based studies from the USA, where SC-mature BCL significantly outnumber SC-mature NK/TCL.[30]

As for SCL, extranodal lymphomas of the oral cavity have been scantly reported due to their rarity. In the few retrospective studies available, the leading histopathological subtypes are MALT lymphoma, followed by DLBCL in one cohort, and plasmablastic lymphoma, DLBCL, and PTCL-NOS in decreasing order in another.[15],[16] In our series, one case corresponded to MALT lymphoma and the other to PTCL-NOS, the rarest POL variant reported. No cases of plasmablastic lymphoma were observed though albeit our institution being a major referral center for HIV patients. This could relate to a selection bias in the HIV+ population at our hospital however since most have undetectable viral loads due to successful antiretroviral treatment.

   Conclusions Top

In summary, albeit limitations in our study include the inherent biases of institutional series as opposed to population-based studies, and the inability to recategorize the totality of our cohort, our results support the utility of the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases, and the notion of geographical variances in the rate of lymphomas. In particular, we report that some of the disparity may arise from viral-induced lymphomas which might show partial geographical restriction. The differential rates of oral and cutaneous lymphomas in our population may hold closer similarities to registries from Asian populations than to those from Europe and USA, supporting the concept of individual and/or racial susceptibility. Further, multicentric nationwide prospective epidemiological studies to foster support to our findings are warranted.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Willemze R, Meijer CJ. EORTC classification for primary cutaneous lymphomas: A comparison with the R.E.A.L. Classification and the proposed WHO Classification. Ann Oncol 2000;11 Suppl 1:11-5.  Back to cited text no. 1
Willemze R, Meijer CJ. Rationale of a new classification for the group of primary cutaneous lymphomas. Semin Cutan Med Surg 2000;19:71-7.  Back to cited text no. 2
Willemze R, Meijer CJ. Classification of cutaneous T-cell lymphoma: From Alibert to WHO-EORTC. J Cutan Pathol 2006;33 Suppl 1:18-26.  Back to cited text no. 3
Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al . WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105:3768-85.  Back to cited text no. 4
Burg G, Kempf W, Cozzio A, Feit J, Willemze R, S Jaffe E, et al. WHO/EORTC classification of cutaneous lymphomas 2005: Histological and molecular aspects. J Cutan Pathol 2005;32:647-74.  Back to cited text no. 5
Willemze R. Cutaneous T-cell lymphoma: Epidemiology, etiology, and classification. Leuk Lymphoma 2003;44 Suppl 3:S49-54.  Back to cited text no. 6
Zackheim HS, Vonderheid EC, Ramsay DL, LeBoit PE, Rothfleisch J, Kashani-Sabet M. Relative frequency of various forms of primary cutaneous lymphomas. J Am Acad Dermatol 2000;43(5 Pt 1):793-6.  Back to cited text no. 7
Jenni D, Karpova MB, Seifert B, Golling P, Cozzio A, Kempf W, et al. Primary cutaneous lymphoma: Two-decade comparison in a population of 263 cases from a Swiss tertiary referral centre. Br J Dermatol 2011;164:1071-7.  Back to cited text no. 8
Vilar Coromina N, Marcos-Gragera R. Primary cutaneous lymphomas. Population-based incidence and survival, 1994-2004. Med Clin (Barc) 2008;131:396-7.  Back to cited text no. 9
Riou-Gotta MO, Fournier E, Mermet I, Pelletier F, Humbert P, Danzon A, et al. Primary cutaneous lymphomas: A population-based descriptive study of 71 consecutive cases diagnosed between 1980 and 2003. Leuk Lymphoma 2008;49:1537-44.  Back to cited text no. 10
Sirsath NT, Lakshmaiah KC, Das U, Lokanatha D, Chennagiri SP, Ramarao C. Primary extranodal non-Hodgkin's lymphoma of oral cavity – A single centre retrospective study. J Cancer Res Ther 2014;10:945-50.  Back to cited text no. 11
Shah GH, Panwar SK, Chaturvedi PP, Kane SN. Isolated primary extranodal lymphoma of the oral cavity: A series of 15 cases and review of literature from a tertiary care cancer centre in India. Indian J Med Paediatr Oncol 2011;32:76-81.  Back to cited text no. 12
[PUBMED]  [Full text]  
Sato Y, Onishi N, Morito T, Takata K, Mizobuchi K, Nagatsuka H, et al. Patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma exhibit favorable prognosis despite a non-germinal center B-cell-like phenotype. Cancer Sci 2009;100:42-6.  Back to cited text no. 13
Boulaadas M, Benazzou S, Sefiani S, Nazih N, Essakalli L, Kzadri M. Primary extranodal non-Hodgkin lymphoma of the oral cavity. J Craniofac Surg 2008;19:1183-5.  Back to cited text no. 14
van der Waal RI, Huijgens PC, van der Valk P, van der Waal I. Characteristics of 40 primary extranodal non-Hodgkin lymphomas of the oral cavity in perspective of the new WHO classification and the International Prognostic Index. Int J Oral Maxillofac Surg 2005;34:391-5.  Back to cited text no. 15
Wolvius EB, van der Valk P, van der Wal JE, van Diest PJ, Huijgens PC, van der Waal I, et al. Primary extranodal non-Hodgkin lymphoma of the oral cavity. An analysis of 34 cases. Eur J Cancer B Oral Oncol 1994;30B: 121-5.  Back to cited text no. 16
Takahashi H, Fujita S, Okabe H, Tsuda N, Tezuka F. Immunophenotypic analysis of extranodal non-Hodgkin's lymphomas in the oral cavity. Pathol Res Pract 1993;189:300-11.  Back to cited text no. 17
Takahashi H, Tsuda N, Tezuka F, Okabe H. Primary extranodal non-Hodgkin's lymphoma of the oral region. J Oral Pathol Med 1989;18:84-91.  Back to cited text no. 18
Takahashi H, Tezuka F, Fujita S, Okabe H. Primary extranodal non-Hodgkin's malignant lymphoma of the oral region: Analysis of 11 autopsy cases. J Oral Pathol 1987;16:241-50.  Back to cited text no. 19
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.  Back to cited text no. 20
Khan G, Hashim MJ. Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010. Infect Agent Cancer 2014;9:38.  Back to cited text no. 21
Skrabek P, Turner D, Seftel M. Epidemiology of non-Hodgkin lymphoma. Transfus Apher Sci 2013;49:133-8.  Back to cited text no. 22
Takino H, Li C, Hu S, Kuo TT, Geissinger E, Muller-Hermelink HK, et al. Primary cutaneous marginal zone B-cell lymphoma: A molecular and clinicopathological study of cases from Asia, Germany, and the United States. Mod Pathol 2008;21:1517-26.  Back to cited text no. 23
Izarzugaza MI, Steliarova-Foucher E, Martos MC, Zivkovic S. Non-Hodgkin's lymphoma incidence and survival in European children and adolescents (1978-1997): Report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006;42:2050-63.  Back to cited text no. 24
Peh SC, Poppema S. Lymphoma: An introduction into historical background, classification schemes, aetiology, geographical variation and epidemiological trend. Malays J Pathol 2001;23:49-63.  Back to cited text no. 25
Pombo De Oliveira MS, Loureiro P, Bittencourt A, Chiattone C, Borducchi D, De Carvalho SM, et al. Geographic diversity of adult t-cell leukemia/lymphoma in Brazil. The Brazilian ATLL Study Group. Int J Cancer 1999;83:291-8.  Back to cited text no. 26
Dal Maso L, Franceschi S, Lo Re A, La Vecchia C. Comparison of the distribution of non-AIDS Kaposi's sarcoma and non-Hodgkin's lymphoma in Europe. Br J Cancer 1999;79:161-3.  Back to cited text no. 27
Imam MH, Shenoy PJ, Flowers CR, Phillips A, Lechowicz MJ. Incidence and survival patterns of cutaneous T-cell lymphomas in the United States. Leuk Lymphoma 2013;54:752-9.  Back to cited text no. 28
Litvinov IV, Tetzlaff MT, Rahme E, Jennings MA, Risser DR, Gangar P, et al. Demographic patterns of cutaneous T-cell lymphoma incidence in Texas based on two different cancer registries. Cancer Med 2015;4:1440-7.  Back to cited text no. 29
Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: A population-based study of 3884 cases. Blood 2009;113:5064-73.  Back to cited text no. 30
Chang D, Zerbini MC, Sotto MN, Siqueira SA, Sanches JA. Evaluation of the 2008 World Health Organization classification for non-mycosis fungoides, non-Sezary syndrome T/NK-cell lymphomas with primary cutaneous involvement. J Cutan Pathol 2015;42:965-73.  Back to cited text no. 31
Nudelmann LM, Bonamigo RR. Primary cutaneous lymphoma in Southern Brazil: A 12-year single-center experience. Int J Dermatol 2015;54:e512-20.  Back to cited text no. 32
Bittencourt AL, Oliveira PD, Andrade AC, Santos TC, Oliveira RF, Farré L, et al. Analysis of cutaneous lymphomas in a medical center in Bahia, Brazil. Am J Clin Pathol 2013;140:348-54.  Back to cited text no. 33
Bittencourt AL, da Graças Vieira M, Brites CR, Farre L, Barbosa HS. Adult T-cell leukemia/lymphoma in Bahia, Brazil: Analysis of prognostic factors in a group of 70 patients. Am J Clin Pathol 2007;128:875-82.  Back to cited text no. 34
Pombo de Oliveira MS, Matutes E, Schulz T, Carvalho SM, Noronha H, Reaves JD, et al. T-cell malignancies in Brazil. Clinico-pathological and molecular studies of HTLV-I-positive and -negative cases. Int J Cancer 1995;60:823-7.  Back to cited text no. 35
Rodríguez-Pinilla SM, Barrionuevo C, Garcia J, Martínez MT, Pajares R, Montes-Moreno S, et al. EBV-associated cutaneous NK/T-cell lymphoma: Review of a series of 14 cases from peru in children and young adults. Am J Surg Pathol 2010;34:1773-82.  Back to cited text no. 36
Barrionuevo C, Anderson VM, Zevallos-Giampietri E, Zaharia M, Misad O, Bravo F, et al. Hydroa-like cutaneous T-cell lymphoma: A clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. Appl Immunohistochem Mol Morphol 2002;10:7-14.  Back to cited text no. 37
Del Aguila R, Gimenez L, Molinari M, Spirelli C, Zanassi M, Perduca S, et al . Retrospective Study of Cutaneous Lymphomas Relationship with WHO/EORTC Classification. In: Book of Abstracts of 21st World Congress of Dermatology. Buenos Aires, Argentina: International League of Dermatological Societies; 2007.  Back to cited text no. 38
Hassan ML, Oro G, Sanz I, Chaparro E, Schroh RG, Corbella C et al . T-cell Cutaneous Lymphomas: A 16-Year Study. In: Book of Abstracts of 21st World Congress of Dermatology. Buenos Aires, Argentina: International League of Dermatological Societies; 2007.   Back to cited text no. 39
Beltrán-Gárate B, Morales-Luna D, Quiñones-Ávila P, Hurtado de Mendoza F, Riva-Gonzalez L, Yabar-Berocal A, et al . Linfomas cutáneos primários: Estúdio retrospectivo clinicopatológico durante el período 1997-2004 en el hospital edgardo rebagliati martins, Essalud, Lima, Perú. Acta Med Peru 2008;25:81-4.  Back to cited text no. 40
Bellei M, Chiattone CS, Luminari S, Pesce EA, Cabrera ME, de Souza CA, et al. T-cell lymphomas in South America and Europe. Rev Bras Hematol Hemoter 2012;34:42-7.  Back to cited text no. 41
Bessell EM, Humber CE, O'Connor S, English JS, Perkins W, Dickinson PD, et al. Primary cutaneous B-cell lymphoma in Nottinghamshire U.K.: Prognosis of subtypes defined in the WHO-EORTC classification. Br J Dermatol 2012;167:1118-23.  Back to cited text no. 42
Chihara D, Ito H, Matsuo K. Comparison of the incidence and trends of hematologic malignancies between Japan and the United States. Rinsho Ketsueki 2015;56:366-74.  Back to cited text no. 43
Han JH, Ko YH, Kang YK, Kim WS, Kim YJ, Kim I, et al. Characteristics of cutaneous lymphomas in Korea according to the new WHO-EORTC classification: Report of a nationwide study. Korean J Pathol 2014;48:126-32.  Back to cited text no. 44
Liu J, Yu X, Liu Y, Jin H, Ma D, Qu T, et al. Relative frequency and survival of primary cutaneous lymphomas: A retrospective analysis of 98 patients. Chin Med J (Engl) 2014;127:645-50.  Back to cited text no. 45
Hamada T, Iwatsuki K. Cutaneous lymphoma in Japan: A nationwide study of 1733 patients. J Dermatol 2014;41:3-10.  Back to cited text no. 46
Liao JB, Chuang SS, Chen HC, Tseng HH, Wang JS, Hsieh PP. Clinicopathologic analysis of cutaneous lymphoma in taiwan: A high frequency of extranodal natural killer/t-cell lymphoma, nasal type, with an extremely poor prognosis. Arch Pathol Lab Med 2010;134:996-1002.  Back to cited text no. 47
Tan SH, Sim CS, Ong BH. Cutaneous lymphomas other than mycosis fungoides in Singapore: A clinicopathological analysis using recent classification systems. Br J Dermatol 2003;149:542-53.  Back to cited text no. 48
Xu ZG, Iwatsuki K, Ohtsuka M, Oyama N, Matsui T, Kaneko F. Polymorphism analysis of Epstein-Barr virus isolates from patients with cutaneous natural killer/T-cell lymphoproliferative disorders: A possible relation to the endemic occurrence of these diseases in Japan. J Med Virol 2000;62:239-46.  Back to cited text no. 49
Góngora-Biachi RA, González-Martínez P, Castro-Sansores C, Bastarrachea-Ortiz J. Infection with HTLV virus type I-II in patients with cervico-uterine cancer in the Yucatan peninsula, Mexico. Ginecol Obstet Mex 1997;65:141-4.  Back to cited text no. 50
Zapata-Benavides P, Lara-Rodríguez MA, Alcocer-González JM, Rodríguez-Padilla C, Taméz-Guerra R, Trejo-Avila LM. Seroprevalence of HTLV-I/II in different groups at risk in northeast Mexico. Vox Sang 1996;70:181-2.  Back to cited text no. 51
Gongora-Biachi RA, Gonzalez-Martinez P, Castros-Sansores C, Pavia-Ruz N, Rudolph DL, Lal RB. Human T lymphotropic virus type II (HTLV-II) infection among female prostitutes in Yucatan, Mexico. Am J Med Sci 1993;306:207-11.  Back to cited text no. 52
Sierra Madero JG, Ponce de León S, Ruiz Palacios G, Tinoco JC, Calva JJ, Zamora EE. Prevalence of antibodies against the lymphadenopathy-associated virus/human T-cell lymphotropic virus type III (LAV/HTLV) in a population of homosexuals in Mexico. Salud Publica Mex 1986;28:180-5.  Back to cited text no. 53
Bandeira LM, Uehara SN, Asato MA, Aguena GS, Maedo CM, Benites NH, et al. High prevalence of HTLV-1 infection among Japanese immigrants in non-endemic area of Brazil. PLoS Negl Trop Dis 2015;9:e0003691.  Back to cited text no. 54
Ishitsuka K, Yamano Y, Utsunomiya A, Uchimaru K. A survey of HTLV-1 carrier clinics in Japan. Rinsho Ketsueki 2015;56:666-72.  Back to cited text no. 55
Xie J, Ge S, Zhang Y, Lin Y, Ni H, Zhang J, et al. The prevalence of human T-lymphotropic virus infection among blood donors in Southeast China, 2004-2013. PLoS Negl Trop Dis 2015;9:e0003685.  Back to cited text no. 56
James E, Sokhn JG, Gibson JF, Carlson K, Subtil A, Girardi M, et al. CD4 + primary cutaneous small/medium-sized pleomorphic T-cell lymphoma: A retrospective case series and review of literature. Leuk Lymphoma 2015;56:951-7.  Back to cited text no. 57
Williams VL, Torres-Cabala CA, Duvic M. Primary cutaneous small- to medium-sized CD4+ pleomorphic T-cell lymphoma: A retrospective case series and review of the provisional cutaneous lymphoma category. Am J Clin Dermatol 2011;12:389-401.  Back to cited text no. 58
Beltraminelli H, Leinweber B, Kerl H, Cerroni L. Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma: A cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases. Am J Dermatopathol 2009;31:317-22.  Back to cited text no. 59
Charli-Joseph Y, Saeb-Lima M, Hernández-Salazar A, Domínguez-Cherit J. Nasal-type extranodal natural killer/T-cell lymphoma presenting as genital ulcers. J Am Acad Dermatol 2012;67:e157-9.  Back to cited text no. 60
Lee WJ, Won KH, Won CH, Chang SE, Choi JH, Moon KC, et al. Secondary cutaneous lymphoma: Comparative clinical features and survival outcome analysis of 106 cases according to lymphoma cell lineage. Br J Dermatol 2015;173:134-45.  Back to cited text no. 61

What is new?

  • The relative frequencies of cutaneous and oral lymphomas in the first Mexican cohort hold closer similarities to Asian registries than from those of Europe and USA.
  • International geographical disparities in the rate of cutaneous lymphomas may arise from viral-induced lymphomas which might show partial geographical restriction.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]

  [Table 1], [Table 2], [Table 3]


Print this article  Email this article
    Similar in PUBMED
 Related articles
    Article in PDF (3,308 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

    Materials and Me...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded4    
    Comments [Add]    

Recommend this journal